Registration Dossier

Administrative data

Endpoint:
dermal absorption in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study run to international guideline but not GLP, but published in a peer reviewed journal.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2002
Report Date:
2002

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 428 (Skin Absorption: In Vitro Method)
Deviations:
not specified
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline
Details on test material:
- Name of test material (as cited in study report): HMX
- Substance type: explosive
- Physical state: crystalline powder
- Radiochemical purity (if radiolabelling): 97.7%
- Specific activity (if radiolabelling): 6.84 mCi/mmol
- Locations of the label (if radiolabelling): ring- 14C
Radiolabelling:
yes

Test animals

Species:
pig
Strain:
other: Yorkshire
Sex:
female

Administration / exposure

Type of coverage:
open
Vehicle:
acetone
Duration of exposure:
24 h
Doses:
10 μg/cm2
Details on in vitro test system (if applicable):
SKIN PREPARATION
- Source of skin: female Yorkshire pigs
- Type of skin: whole skin from upper back of pig
- Preparative technique: dermatomed
- Thickness of skin (in mm): 0.5-0.9 mm
- Membrane integrity check: no but under same conditions, pigskin shown to maintain viability for at least 50h (Reifenrath and Hawkins, 1986)
- Storage conditions: 12 h at 4°C

PRINCIPLES OF ASSAY
- Diffusion cell: stainless-steel version of the low volume flow cell (Reifenrath et al, 1994)
- Receptor fluid: RPMI tissue culture medium
- Solubility of test substance in receptor fluid: unknown
- Static system: yes
- Flow-through system: no
- Test temperature: unknown
- Humidity: unknown
- Occlusion: no
- Reference substance(s): no


- Reifenrath, W. G., Lee, B., Wilson, D. R., and Spencer, T. S. (1994). A comparison of in vitro skin-penetration cells. J. Pharm. Sci. 83, 1229–1233.
- Reifenrath, W. G., and Hawkins, G. S. (1986). The weanling Yorkshire pig as an animal model for measuring percutaneous penetration. In Swine in
Biomedical Research, 1st ed. (M. E. Tumbleson, Ed.), pp. 673–680. Plenum, New York.

Results and discussion

Signs and symptoms of toxicity:
not specified
Dermal irritation:
not specified
Absorption in different matrices:
- Receptor fluid : 0.1 ± 0.1% of applied radioactive dose
- Epidermis : 16 ± 4% of applied radioactive dose
- Dermis : 3 ± 2% of applied radioactive dose
- Stratum corneum : 73 ± 8% of applied radioactive dose
- Evaporation : 0.09 ± 0.02% of applied radioactive dose
Total recovery:
- Total recovery: 97 ± 3% of applied radioactive dose
Percutaneous absorption
Dose:
10 μg/cm2
Parameter:
percentage
Absorption:
4 %
Remarks on result:
other: 24 h

Applicant's summary and conclusion

Conclusions:
The percentage of absorption of HMX in acetone in an in vitro pig skin absorption method was 4%